Browsing by Author "Emmert, Birgit"

CONTEXT The dissemination of objective structured clinical examinations (OSCEs) is hampered by requirements for high levels of staffing and a significantly higher workload compared with multiple-choice examinations. Senior medical students may be able to support faculty staff to assess their peers. The aim of this study is to assess the reliability of student tutors as OSCE examiners and their acceptance by their peers. METHODS Using a checklist and a global rating, teaching doctors (TDs) and student tutors (STs) simultaneously assessed students in basic clinical skills at 4 OSCE stations. The inter-rater agreement between TDs and STs was calculated by kappa values and paired t-tests. Students then completed a questionnaire to assess their acceptance of student peer examiners. RESULTS All 214 Year 3 students at the University of Gottingen Medical School were evaluated in spring 2005. Student tutors gave slightly better average grades than TDs (differences of 0.02-0.20 on a 5-point Likert scale). Inter-rater agreement at the stations ranged from 0.41 to 0.64 for checklist assessment and global ratings; overall inter-rater agreement on the final grade was 0.66. Most students felt that assessment by STs would result in the same grades as assessment by TDs (64%) and that it would be similarly objective (69%). Nearly all students (95%) felt confident that they could evaluate their peers themselves in an OSCE. CONCLUSIONS On the basis of our results, STs can act as examiners in summative OSCEs to assess basic medical skills. The slightly better grades observed are of no practical concern. Students accepted assessment performed by STs.

The use of veterinary medicines and medicated feed has a potential for the exposure of agricultural workers to pharmaceuticals with phototoxic and photoallergic side-effects. We present a 67-year-old self-employed farmer and pig breeder with a 22-year history of severe persistent photosensitivity following photoallergic contact dermatitis due to direct occupational dermal and airborne contact to chlorpromazine (sedative) and olaquindox (antibiotic and animal growth promoter, AGP). His first dermatitis symptoms appeared at the age of 45 when the pig breeding was intensified. He showed erythematons, scaly, and pruritic plaques localized symmetrically on the sun-exposed backs of his hands, fingers, and forearms, spreading to his face and other sun-exposed body sites. Without protective measures, he injected the animals with chlorpromazine. Besides, for several years he mixed by hand a powder containing olaquindox into the pigs' dry food. Epicutaneous and photo-patch tests showed positive reactions to promethazine, chlorpromazine, and olaquindox. In spite of the complete avoidance of the identified photoallergens for several years, his life is still extremely disabled due to the persistent photosensitivity. Our case report stresses the observation that olaquindox and chlorpromazine as phototoxic agents and photoallergens are capable of inducing a persistent and severe photosensitivity for many years, even after termination of exposure. Although the use of phenothiazine derivates and APGs for animals has meanwhile been banned in the European Union (EU), AGPs are still widely used in Asia. Physicians, especially occupational physicians, should be still aware of these phototoxic and photoallergic agents to reduce the burden of skin disease at work.

In Germany, the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF; consortium of scientific medical societies) constitutes the umbrella organisation to conceive, evaluate, and release guidelines. There are 3 stages of development (S1-S3) according to the evidence level and the process of consensus finding. Currently, 59 dermatologic guidelines have been published under the auspices of the Deutsche Dermatologische Gesellschaft (German Dermatological Society). The guideline for the management of hand dermatitis (AWMF-Register-No: 013/053) is an instructive recent example. This guideline clearly demonstrates the benefits of guidelines, i.e. standardized definition of heterogeneous diseases and disease severity as well as standardized therapy algorithms. This is especially important in diseases difficult-to-treat like chronic hand dermatitis. The effective implementation of guidelines with early incorporation of new therapies, for example alitretinoin in the therapy of hand dermatitis, can considerably improve the quality of life of patients.

Deficiencies in individual DNA repair systems are involved in both de novo and therapy-related acute myeloid leukaemia (t-AML), as indicated by genetic markers involving nucleotide excision repair (NER gene polymorphisms), double-strand-break (DSB) or mismatch repair (microsatellite instability (MSI)). We modified a host cell reactivation (HCR) assay for functional DNA repair system analysis of living primary haematopoietic cells; 2 x 10(5) normal peripheral blood lymphocytes (PBLs) and cord blood CD34+ progenitor cells were cryopreserved, thawed and transfected with 75 250 ng luciferase reporter plasmid (pCMVLuc) using DEAE-dextran (0.1 mg/mL) in a transfection volume of 250 mu L. We obtained luciferase activities of similar to 300-fold above background in CD34+ progenitor cells and similar to 2000-fold in PBLs, thus rendering these cells applicable for DNA repair analysis. We then evaluated the NER (UV-irradiated pCMVLuc) and DSB repair capacity (linearized pCMVLuc) of normal lymphocytes and several leukaemic cell lineages. Kasumi-1 and HL-60 AML cells exhibited a reduced NER capacity compared to normal GM03715 lymphocytes, PBLs and CD34+ progenitor cells (6.2 +/- 0.9 %, 6.5 +/- 0.9% vs. 12.3 +/- 1.8 %, 13.5 +/- 0.7% and 13.5 +/- 2.0 %, respectively). Kasumi-1 AML cells exhibited a reduced DSB repair capacity compared to AG10107 and GM03715 normal lymphocytes as well as CEM acute T-cell lymphoblastic leukaemia cells (6.4 +/- 0.8% vs. 10.8 +/- 0.7 %, 27.3 +/- 1.1% and 20.5 +/- 1.6 %, respectively). The modified HCR assay can be used for functional DNA repair analysis in living cells of patients with pre- and post-leukaemic conditions as well as in leukaemic blasts to elucidate the role of DNA repair in de novo and t-AML leukaemogenesis and to determine the individual susceptibility to t-AML prior to chemotherapy.

Poor metabolic competence of in vitro systems was proposed to be one of their major shortcomings accounting for false negative results in genotoxicity testing. For several "low molecular weight cancer suspects" this was specifically attributed to the lack of cytochrome P450 2E1 (CYP2E1) in conventional in vitro metabolising systems. One promising attempt to overcome this problem is the transfection of "methyltransferase-deficient" S. typhimurium strains with the plasmid pin3ERb(5). This plasmid contains DNA encoding for a complete electron transport chain, comprising P450 reductase, cytochrome b(5) and cytochrome P450 2E1 In order to answer the question if CYP2E1 substrates that yield negative or inconclusive results in the Ames test can be activated by metabolic competent bacterial strains, we used YG7108pin3ERb(5) to investigate the following compounds: acetamide, acrylamide, acrylonitrile, allyl chloride, ethyl acrylate, ethyl carbamate, methyl-methacrylate, vinyl acetate, N-nitrosopyrrolidine, trichloroethylene and tetrachloroethylene. N-Nitrosodiethylamine served as a positive control. In addition to these known or proposed CYP2E1 substrates, we investigated the polycyclic aromatic hydrocarbon benzo[a]pyrene and the heterocyclic aromatic amines 2-aminofluorene and 2-aminoanthracene. Results: The extensive metabolic competence of the transformed strain is underlined by results showing strong mutagenicity between 10 and 500 mu g N-nitrosopyrrolidine per plate. Unexpectedly, 2-aminoanthracene was mutagenic at a concentration range between 25 and 250 mu g per plate using YG7108pin3ERb(5). Moreover, we demonstrate for the first time a clear response of sufficiently characterised allyl chloride in the Ames test at a reasonably low concentration range between 300 and 1500 mu g per plate. We achieved similar results in the parent strain YG7108 with conventional metabolic activation. Without metabolic activation less pronounced mutagenicity occurred, suggesting a contribution of a direct alkylating effect. Propylene oxide is usually contained in allyl chloride as stabilizer at amounts up to 0.09%. Though YG7108 revealed to be very sensitive towards propylene oxide, allyl chloride dissolved in water was not mutagenic, showing that no water soluble compounds contribute to its mutagenicity. None of the remaining compounds showed mutagenic effects using YG7108pin3ERb(5).

Diesel engine emissions (DEE) are classified as probably carcinogenic to humans. In recent years every effort was made to reduce DEE and their content of carcinogenic and mutagenic polycyclic aromatic compounds. Since 1995 we observed an appreciable reduction of mutagenicity of DEE driven by reformulated or newly designed fuels in several studies. Recently, the use of rapeseed oil as fuel for diesel engines is rapidly growing among German transportation businesses and agriculture due to economic reasons. We compared the mutagenic effects of DEE from two different batches of rapeseed oil (RSO) with rapeseed methyl ester (RME, biodiesel), natural gas derived synthetic fuel (gas-to-liquid, GTL), and a reference diesel fuel (DF). The test engine was a heavy-duty truck diesel running the European Stationary Cycle. Particulate matter from the exhaust was sampled onto PTFE-coated glass fibre filters and extracted with dichloromethane in a soxhlet apparatus. The gas phase constituents were sampled as condensates. The mutagenicity of the particle extracts and the condensates was tested using the Salmonella typhimurium/mammalian microsome assay with tester strains TA98 and TA100. Compared to DF the two RSO qualities significantly increased the mutagenic effects of the particle extracts by factors of 9.7 up to 59 in tester strain TA98 and of 5.4 up to 22.3 in tester strain TA100, respectively. The condensates of the RSO fuels caused an up to factor 13.5 stronger mutagenicity than the reference fuel. RME extracts had a moderate but significant higher mutagenic response in assays of TA98 with metabolic activation and TA100 without metabolic activation. GTL samples did not differ significantly from DF. In conclusion, the strong increase of mutagenicity using RSO as diesel fuel compared to the reference DF and other fuels causes deep concern on future usage of this biologic resource as a replacement of established diesel fuels.

The recessively inherited nucleotide excision repair (NER) defect syndrome xeroderma pigmentosum (XP) serves as a model disease for UV-induced skin cancer. XP is characterized by sun-sensitivity, freckling, and poikilodermic skin changes in sun-exposed areas, and a more than 1000-fold increased risk of skin cancer including melanoma as well as basal and squamous cell carcinomas. Seven XP complementation groups (XP-A to XP-G) are known to date representing the defective genes in XP patients. An additional "variant" form (XPV) which is clinically indistinguishable from the complementation groups exhibits defective translesional synthesis. An enhanced understanding of skin cancer development in general can help to identify individuals at an increased risk who should take special precautions, for example to avoid occupational exposures. The position of skin cancer induced by UV-light as an occupational disease in the ordinance on industrial diseases (BKV) is currently a topic of research and discussion in Germany.